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Circulation. 2019;139:e1082–e1143. DOI: 10.1161/CIR.0000000000000625 June 18/25, 2019 e1083 CLINICAL STATEMENTS AND GUIDELINES

TABLE OF CONTENTS

Top 10 Take-Home Messages to Reduce Risk of Atherosclerotic Cardiovascular Disease Through Cholesterol Management . . . . . . . . . . . . . . . . . . . . e1083 Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e1084 1.	Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e1085 1.1.	 Methodology and Evidence Review . . . . . . . . . e1085 1.2.	 Organization of the Writing Committee . . . . . e1086 1.3.	 Document Review and Approval . . . . . . . . . . . e1086 1.4.	 Scope of the Guideline . . . . . . . . . . . . . . . . . . e1086 1.5.	 Class of Recommendation and Level of Evidence . . . . . . . . . . . . . . . . . . . . . . . . . . . e1087 1.6.	 Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . e1087 2.	High Blood Cholesterol and ASCVD . . . . . . . . . . . . e1087 2.1.	 Serum Cholesterol, Lipoproteins, and ASCVD . . e1087 2.1.1.	Cholesterol, Lipoproteins, and Apolipoprotein B . . . . . . . . . . . . . . . . . e1087 2.1.2.	Cholesterol, LDL-C, and ASCVD . . . . . . e1087 2.1.3.	LDL-C and Other Risk Factors . . . . . . . . e1087 2.2.	 Measurements of LDL-C and Non–HDL-C . . . . e1088 2.3.	 Measurements of Apolipoprotein B and Lipoprotein (a) . . . . . . . . . . . . . . . . . . . . . e1089 2.4.	 Monitoring Response of LDL-C to Statin Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e1090 3.	Therapeutic Modalities . . . . . . . . . . . . . . . . . . . . . . e1090 3.1.	 Lifestyle Therapies . . . . . . . . . . . . . . . . . . . . . e1090 3.1.1.	Diet Composition, Weight Control, and Physical Activity . . . . . . . . . . . . . . . e1090 3.1.2.	Lifestyle Therapies and Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . e1090 3.2.	 Lipid-Lowering Drugs . . . . . . . . . . . . . . . . . . . e1090 3.2.1.	Statin Therapy . . . . . . . . . . . . . . . . . . . e1090 3.2.2.	Nonstatin Therapies . . . . . . . . . . . . . . . e1091 3.2.3.	Nonstatin Add-on Drugs to Statin Therapy . . . . . . . . . . . . . . . . . . . . . . . . e1091 4.	Patient Management Groups . . . . . . . . . . . . . . . . . e1091 4.1.	 Secondary ASCVD Prevention . . . . . . . . . . . . . e1091 4.2.	 Severe Hypercholesterolemia (LDL-C ≥190 mg/dL [≥4.9 mmol/L]) . . . . . . . . . . . . . . e1095 4.3.	 Diabetes Mellitus in Adults . . . . . . . . . . . . . . . e1097 4.4.	 Primary Prevention . . . . . . . . . . . . . . . . . . . . . e1099 4.4.1.	Evaluation and Risk Assessment . . . . . . e1099 4.4.2.	 Primary Prevention Adults 40 to 75 Years of Age With LDL-C Levels 70 to 189 mg/dL (1.7 to 4.8 mmol/L) . . . e1102 4.4.3.	Monitoring in Response to LDL-C–Lowering Therapy . . . . . . . . . . . e1106 4.4.4.	Primary Prevention in Other Age Groups . . . . . . . . . . . . . . . . . . . . . . . . . e1107 4.5.	 Other Populations at Risk . . . . . . . . . . . . . . . . e1111 4.5.1.	Ethnicity . . . . . . . . . . . . . . . . . . . . . . . . e1111 4.5.2.	Hypertriglyceridemia . . . . . . . . . . . . . . e1112 5.	Statin Safety and Statin-Associated Side Effects . . . e1117 6.	Implementation . . . . . . . . . . . . . . . . . . . . . . . . . . . e1120 7.	Cost and Value Considerations . . . . . . . . . . . . . . . . e1121 7.1.	 Economic Value Considerations: PCSK9 Inhibitors . . . . . . . . . . . . . . . . . . . . . . . e1121 8.	Limitations and Knowledge Gaps . . . . . . . . . . . . . . e1122 8.1.	 Randomized Controlled Trials . . . . . . . . . . . . . e1122 8.2.	 Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . e1122 8.2.1.	Continuing Refinement of PCE . . . . . . . e1123 8.2.2.	Improvement in Lifetime Risk Estimate . . e1123 8.2.3.	Refinement of Clinician–Patient Risk Discussion . . . . . . . . . . . . . . . . . . . . . . e1123 8.2.4.	Monitoring and Adjustment of Treatment . . . . . . . . . . . . . . . . . . . . e1123 8.2.5.	Prognostic Significance of CAC . . . . . . e1123 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e1124 Appendix 1: Author Relationships With Industry

and Other Entities (Relevant)—2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol (August 2018)�����������������������������������������e1139 Appendix 2: Reviewer Relationships With Industry

and Other Entities (Comprehensive)—2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol (August 2018)�����������������������������������������e1141

TOP 10 TAKE-HOME MESSAGES TO REDUCE RISK OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE THROUGH CHOLESTEROL MANAGEMENT

1.	 In all individuals, emphasize a heart-healthy lifestyle across the life course. A healthy lifestyle reduces atherosclerotic cardiovascular disease (ASCVD) risk at all ages. In younger individuals, healthy lifestyle can reduce development of risk factors and is the foundation of ASCVD risk reduction. In young adults 20 to 39 years of age, an assessment of lifetime risk facilitates the clinician–patient risk discussion (see No. 6) and emphasizes intensive lifestyle efforts. In all age groups, lifestyle therapy is the primary intervention for metabolic syndrome. 2.	 In patients with clinical ASCVD, reduce lowdensity lipoprotein cholesterol (LDL-C) with high-intensity statin therapy or maximally tolerated statin therapy. The more LDL-C is reduced on statin therapy, the greater will be subsequent risk reduction. Use a maximally tolerated statin to lower LDL-C levels by ≥50%. 3.	 In very high-risk ASCVD, use a LDL-C threshold of 70 mg/dL (1.8 mmol/L) to consider addition of nonstatins to statin therapy. Very high-risk includes a history of multiple major ASCVD events or 1 major ASCVD event and multiple high-risk conditions. In very high-risk ASCVD patients, it is reasonable to add ezetimibe to maximally tolerated statin therapy when the LDL-C level remains ≥70 mg/dL (≥1.8 mmol/L). In patients at very high risk whose LDL-C level

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